The Federal Womens Study is an active clinical protocol aimed at recruiting 360 federal employees and contractors working in the Washington DC metropolitan area. Seventy-six women (54% African-American, 18% African immigrant and 28% white) have been screened and 66 were enrolled (age 459, range 24-62 years). Anemia was the most common reason that screened women were not enrolled. Among the enrolled women, the three groups are well matched by race/ethnicity for age and body mass index and key socio-economic and demographic risk factors such as annual income, educational attainment, family history of diabetes and physical activity. Yet, we have already identified pre-diabetes in 33% of women. Therefore, this cohort reflects women who are at high risk for diabetes and heart disease and an excellent group in which to (a) test the efficacy of existing screening tests and (b) understand the pathophysiological progression of cardiometabolic disease. Since current cardiometabolic screening tests are centered on triglyceride and fasting glucose concentrations, we have employed two approaches to examine these risk factors. The Relationship of Triglycerides with Insulin Resistance and Hyperinsulinemia This study will compare by race and continent of origin, the relationship of triglyceride concentration to key cardiometabolic risk factors, specifically diet, physical activity, insulin resistance (and hyperinsulinemia) and hepatic fat content. Consistent with our hypothesis, fasting triglyceride concentrations are already lower in the African descent than white women (6532 vs. 7831, P=<0.05) with a trend for lower insulin sensitivity index (SI: 2.81.6 vs. 3.8 2.3 mU/L-1min-1, P=0.20) and greater acute insulin response to glucose (AIRg: 808635 vs. 565440 mU/L, P=0.1) in African descent compared white women respectively. At present, the sample size is insufficient to determine the relationship of hepatic fat content with any marker of insulin resistance. However, African-American and African immigrant have similar metabolic characteristics (for example, body mass index, visceral fat content, acute insulin response to glucose and insulin sensitivity indices). Compared to white women, both African-American and African immigrant women have exaggerated hypersinsulinemia. Therefore the rate of progression to prediabetes then diabetes may differ by race. Plans are underway to develop prospective protocols that will elucidate the importance of race/ethnicity in the rate of progression from normal glucose tolerance to prediabetes and diabetes. To further characterize the contribution of insulin secretion, insulin clearance and prandial gut factors to race/ethnic differences in hyperinsulinemia, we are comparing insulin response to oral, intravenous and prandial glucose loads. Currently, 54 women have completed all three tests and preliminary findings suggest racial differences in early postprandial glucose response. African descent women have paradoxically greater postprandial insulin concentrations but lower glucose response and we are exploring further the quantitative contribution of incretin concentrations to hyperinsulinemia. We plan to continue recruitment and look forward to an expanded dataset with interim analyses of our primary outcome variable, triglyceride concentration, with key modifying factors (diet composition, physical activity, insulin sensitivity indices and hepatic fat) among the three groups.